Ventilator-associated pneumonia (VAP) is an acute care complication with high morbidity and mortality, which is costly in length of stay and resources used. Post-intubation application of chlorhexidine (CHX) to the mouths of critically ill adults reduces risk of VAP. During intubation, organisms may be dragged by the tube from the contaminated oropharynx to the sterile lung, and the endotracheal tube (ET) provides a pathway for direct entry of bacteria from the oropharynx to the lower respiratory tract. However, procedures to decontaminate the mouth before intubation are not routine and little is known about the effects of pre-intubation CHX in critically ill patients. Thus, this proposal focuses on evaluating the benefit of adding a pre-intubation CHX dose to the known benefit of post-intubation CHX to reduce the risk of VAP as measured by Clinical Pulmonary Infection Score (CPIS). In order to examine the effect of pre-intubation CHX on early ET colonization, we also propose quantitative microbial examination of ETs of subjects who are extubated in the first 24 hours of study participation. Further, we intend to explore selected biomarkers (procalcitonin, cytokines) as indicators of development of VAP. The primary aim of this study is to test the effect of a pre-intubation oral application of CHX on the development of VAP in a variety of mechanically ventilated, critically ill adults. Secondary aims are 1) to test the effect of a pre-intubation oral application of CHX on early ET colonization in mechanically ventilated adults, and 2) to explore potential biomarkers of VAP development and resolution. Adults undergoing endotracheal intubation (n=325) will be randomized to pre-intubation intervention (CHX gluconate 0.12% solution) or control. All subjects will receive CHX post-intubation. Effect of CHX on risk of VAP (CPIS score) will be compared using a two-group analysis of covariance (ANCOVA) model with initial CPIS as a covariate. Effect of CHX on log-transformed cfu/ml from ETs removed in the first 24 hours after intubation will similarly be tested using an ANCOVA model with time to extubation as a covariate. Biomarkers will be evaluated in a subset of 100 subjects using a repeated measures regression model, regressing biomarkers against CPIS. The project will add to knowledge about the relationships among oral health, ET intubation and VAP, and addresses an important clinical outcome. Pre-intubation oral decontamination could reduce risk of VAP and its associated morbidity and mortality. PUBLIC HEALTH RELEVANCE Ventilator-associated pneumonia is a serious complication in mechanically ventilated critically ill patients. The intervention tested in this project (swabbing the mouth with chlorhexidine before the endotracheal tube is inserted) could reduce the risk of ventilator-associated pneumonia.